ArticleFrontiers in cell and developmental biology2021
The Regulatory NOD-Like Receptor NLRC5 Promotes Ganglion Cell Death in Ischemic Retinopathy by Inducing Microglial Pyroptosis.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 29 citations in OpenAlex.
- IRF1-mediated sensing of oxidized mitochondrial DNA drives macrophage PANoptosis in lung ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2026Article
- PARP1 inhibition in naïve mouse embryonic stem cells induces viral mimicry.Nucleic acids research · 2026Article
- NLRC5-Mediated Epigenetic and Proteomic Regulation of Microglial Panoptosis Drives Neuroinflammation in Multiple Sclerosis.Molecular neurobiology · 2025Article
- Microglial NLRC5 drives lysosomal dysfunction to disrupt autophagic flux and promote post-stroke neuroinflammation.Journal of neuroinflammation · 2025Article
- Pyroptosis in gastric mucosal injury‑related diseases (Review).International journal of molecular medicine · 2025Review
- Neferine Targeted the NLRC5/NLRP3 Pathway to Inhibit M1-type Polarization and Pyroptosis of Macrophages to Improve Hyperuricemic Nephropathy.Current molecular medicine · 2025Article
- CCR5-overexpressing mesenchymal stem cells protect against experimental autoimmune uveitis: insights from single-cell transcriptome analysis.Journal of neuroinflammation · 2024Article
- NLRC5 Deficiency Reduces LPS-Induced Microglial Activation via Inhibition of NF-κB Signaling and Ameliorates Mice's Depressive-like Behavior.International journal of molecular sciences · 2023Article
- NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models.Journal of neuroinflammation · 2023Article
- A lncRNA-encoded mitochondrial micropeptide exacerbates microglia-mediated neuroinflammation in retinal ischemia/reperfusion injury.Cell death & disease · 2023Article
- Article
- Host immune responses in the central nervous system during fungal infections.Immunological reviews · 2022Review
- microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection.International journal of molecular sciences · 2022Article
- Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases.Journal of neuroinflammation · 2022Review
- Microglia Polarization: A Novel Target of Exosome for Stroke Treatment.Frontiers in cell and developmental biology · 2022Review
- Targeting Novel Regulated Cell Death: Pyroptosis, Necroptosis, and Ferroptosis in Diabetic Retinopathy.Frontiers in cell and developmental biology · 2022Review
- A Novel Pyroptosis-Related lncRNAs Signature for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma and Its Associations with Immunity.Journal of oncology · 2021Article
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8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinal ischemia is a common pathological event that can result in retinal ganglion cell (RGC) death and irreversible vision loss. The pathogenic mechanisms linking retinal ischemia to RGC loss and visual deficits are uncertain, which has greatly hampered the development of effective treatments. It is increasingly recognized that pyroptosis of microglia contributes to the indirect inflammatory death of RGCs. In this study, we report a regulatory NOD-like receptor, NOD-, LRR- and CARD-containing 5 (NLRC5), as a key regulator on microglial pyroptosis and the retinal ischemia process. Through an in-depth analysis of our recently published transcriptome data, we found that NLRC5 was significantly up-regulated in retina during ischemia-reperfusion injury, which were further confirmed by subsequent detection of mRNA and protein level. We further found that NLRC5 was upregulated in retinal microglia during ischemia, while NLRC5 knockdown significantly ameliorated retinal ischemic damage and RGC death. Mechanistically, we revealed that knockdown of NLRC5 markedly suppressed gasdermin D (GSDMD) cleavage and activation of interleukin-1β (IL-1β) and caspase-3, indicating that NLRC5 promotes both microglial pyroptosis and apoptosis. Notably, we found that NLRC5 directly bound to NLRP3 and NLRC4 in inflammasomes to cooperatively drive microglial pyroptosis and apoptosis mediating retinal ischemic damage. Overall, these findings reveal a previously unidentified key contribution of NLRC5 signaling to microglial pyroptosis under ischemia or hypoxia conditions. This NLRC5-dependent pathway may be a novel therapeutic target for treatment of ischemic retinopathy.
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